title: Clinical review: A review of the clinical consequences of variation in thyroid function within the reference range.
abstract: BACKGROUND
  Overt thyroid disease is associated with profound adverse health outcomes; however, data are conflicting for studies of borderline/subclinical thyroid dysfunction. Many studies of subclinical thyroid disease have had low power and were prone to selection bias. In contrast, large datasets are available from community studies in healthy individuals. Studies of the effects of variation of thyroid function across the reference range on health outcomes in these populations may provide useful information regarding thresholds for treatment of abnormal thyroid function.
  
  
  METHODS
  MEDLINE and the Cochrane Database of Systematic Reviews and Controlled Trials Register were searched for articles studying the effect of variation in thyroid hormone parameters within the reference range on cardiovascular, bone, metabolic, pregnancy, neurological, and psychological outcomes.
  
  
  RESULTS
  Higher TSH/lower thyroid hormone levels are associated with more cardiovascular risk factors and cardiovascular events and worse metabolic parameters and pregnancy outcomes, whereas lower TSH/higher thyroid hormone levels are associated with reduced bone mineral density and increased fracture risk. The evidence base was good for cardiovascular, metabolic, bone, and pregnancy outcomes; however, high-quality data remained lacking for neurological and psychological outcomes.
  
  
  CONCLUSIONS
  Common variation in persons with thyroid function in the normal range are associated with adverse health outcomes. These data suggest, by extrapolation, that carefully monitored treatment of even modest elevations of TSH may have substantial health benefits. Appropriately powered large-scale clinical trials analyzing the risks vs benefits of treating subclinical thyroid disease are required to determine whether these benefits can be achieved with levothyroxine therapy.
authors.affiliation: Thyroid Research Group, Institute of Molecular Medicine, Cardiff University School of Medicine, Cardiff CF14 4XN, United Kingdom.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Taylor
authors.forename: Salman
authors.initials: S
authors.lastname: Razvi
authors.forename: Simon H
authors.initials: SH
authors.lastname: Pearce
authors.forename: Colin M
authors.initials: CM
authors.lastname: Dayan
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D011247:Pregnancy; D011256:Pregnancy Outcome; D012016:Reference Values; D012307:Risk Factors; D013959:Thyroid Diseases / Q000097:blood* / Q000503:physiopathology; D013961:Thyroid Gland / Q000503:physiopathology*; D013963:Thyroid Hormones / Q000097:blood*
chemical_list: D013963:Thyroid Hormones